Pseudobudding: ruptured glands do not represent true tumor buds

Haddad, T. S. et al. (2023) Pseudobudding: ruptured glands do not represent true tumor buds. Journal of Pathology, 261(1), pp. 19-27. (doi: 10.1002/path.6146) (PMID:37403270)

Abstract

Tumor budding (TB) is a strong biomarker of poor prognosis in colorectal cancer and other solid cancers. TB is defined as isolated single cancer cells or clusters of up to four cancer cells at the invasive tumor front. In areas with a large inflammatory response at the invasive front, single cells and cell clusters surrounding fragmented glands are observed appearing like TB. Occurrence of these small groups is referred to as pseudobudding (PsB), which arises due to external influences such as inflammation and glandular disruption. Using a combination of orthogonal approaches, we show that there are clear biological differences between TB and PsB. TB is representative of active invasion by presenting features of epithelial-mesenchymal transition and exhibiting increased deposition of extracellular matrix within the surrounding tumor microenvironment (TME), whereas PsB represents a reactive response to heavy inflammation where increased levels of granulocytes within the surrounding TME are observed. Our study provides evidence that areas with a strong inflammatory reaction should be avoided in the routine diagnostic assessment of TB.

• Item Type: Articles
• Additional Information: This research received funding from the Dutch Cancer Society, project number 10602/2016-2.
• Keywords: Tumor budding, spatial transcriptomics, transmission electron microscopy, immunohistochemistry, pseudobudding, colorectal cancer, multiplex immunofluorescence.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Jamieson, Professor Nigel and Wood, Dr Colin
• Authors: Haddad, T. S., van den Dobbelsteen, L., Öztürk, S. K., Geene, R., Nijman, I. J., Verrijp, K., Jamieson, N. B., Wood, C., van Vliet, S., Reuvers, L., Achouiti, S., Rutgers, N., Brouwer, N., Simmer, F., Zlobec, I., Lugli, A., and Nagtegaal, I. D.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Journal of Pathology
• Publisher: Wiley
• ISSN: 0022-3417
• ISSN (Online): 1096-9896
• Published Online: 04 July 2023
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Journal of Pathology 261(1):19-27
• Publisher Policy: Reproduced under a Creative Commons License